I am a basic researcher in molecular aspects of cancer biology who is interested in salary support to enhance my studies in the role of the tumor suppressor gene p53 in the normal cell and in tumorigenesis. My immediate career goal is to perform basic cancer research by further characterizing a p53-deficient mouse model developed by myself and my collaborators. My long term career goal is to become established as an important contributor in the areas of tumor suppressor genes and animal cancer models. The Research Career Development Award will allow me to intensify my research efforts by freeing grant money to support other personnel and supplies and by reducing the amount of time spent on non- research related activities. The RCDA will further support my development as an independent investigator by allowing me to focus my efforts on pure research activities. The environment in the Division of Molecular Virology at Baylor College of Medicine is extremely supportive of my research efforts. Very good animal facilities, equipment for molecular biology and cell biology studies, specialized core facilities, and access to two student pools (Division of Molecular Virology and Cell and Molecular Biology Program) all provide a very strong infrastructure for research pursuits. The research to be performed in the five year period of support centers on the characterization and exploitation of our p53-deficient mice. We believe that the p53-deficient mouse model provides a powerful tool to study the role of p53 in normal and malignant cells. Our specific aims are first, to further characterize the specific tumors which arise in the p53- deficient mice Special attention will be paid to the frequently occurring lymphomas to understand why loss of p53 predisposes to this particular type of tumor. Second, we will develop other types of specific cancer models through treatment with carcinogens, hormones, or activated oncogenes (via mating to other transgenic mice). Third, we will further analyze the in vitro growth properties of different cell types derived from the p53-deficient mice in an attempt understand the role of p53 loss in stimulating cell growth. Fourth, we will utilize the p53-deficient cells in attempts to identify target genes regulated by p53. Finally, we plan to look at the effects of mutagenic agents on cells lacking p53. Special emphasis will be placed on quantitating mutation rates in the presence and absence of p53.